tetano
Editor, Senior Moderator
NPJ Vaccines
. 2023 May 17;8(1):70.
doi: 10.1038/s41541-023-00664-4. Th[SUB]1[/SUB]-dominant cytokine responses in kidney patients after COVID-19 vaccination are associated with poor humoral responses
Yvette den Hartog[SUP] 1 [/SUP], S Reshwan K Malahe[SUP] 1 [/SUP], Wim J R Rietdijk[SUP] 2 [/SUP], Marjolein Dieterich[SUP] 1 [/SUP], Lennert Gommers[SUP] 3 [/SUP], Daryl Geers[SUP] 3 [/SUP], Susanne Bogers[SUP] 3 [/SUP], Debbie van Baarle[SUP] 4 5 [/SUP], Dimitri A Diavatopoulos[SUP] 6 7 [/SUP], A Lianne Messchendorp[SUP] 8 [/SUP], Renate G van der Molen[SUP] 6 [/SUP], Ester B M Remmerswaal[SUP] 9 [/SUP], Frederike J Bemelman[SUP] 10 [/SUP], Ron T Gansevoort[SUP] 8 [/SUP], Luuk B Hilbrands[SUP] 11 [/SUP], Jan-Stephan Sanders[SUP] 8 [/SUP], Corine H GeurtsvanKessel[SUP] 3 [/SUP], Marcia M L Kho[SUP] 1 [/SUP], Marlies E J Reinders[SUP] 1 [/SUP], Rory D de Vries[SUP] #[/SUP][SUP] 3 [/SUP], Carla C Baan[SUP] #[/SUP][SUP] 12 [/SUP]; RECOVAC Consortium
Affiliations
Cytokines are regulators of the immune response against severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). However, the contribution of cytokine-secreting CD4[SUP]+[/SUP] and CD8[SUP]+[/SUP] memory T cells to the SARS-CoV-2-specific humoral immune response in immunocompromised kidney patients is unknown. Here, we profiled 12 cytokines after stimulation of whole blood obtained 28 days post second 100 μg mRNA-1273 vaccination with peptides covering the SARS-CoV-2 spike (S)-protein from patients with chronic kidney disease (CKD) stage 4/5, on dialysis, kidney transplant recipients (KTR), and healthy controls. Unsupervised hierarchical clustering analysis revealed two distinct vaccine-induced cytokine profiles. The first profile was characterized by high levels of T-helper (Th)[SUB]1[/SUB] (IL-2, TNF-α, and IFN-γ) and Th[SUB]2[/SUB] (IL-4, IL-5, IL-13) cytokines, and low levels of Th[SUB]17[/SUB] (IL-17A, IL-22) and Th[SUB]9[/SUB] (IL-9) cytokines. This cluster was dominated by patients with CKD, on dialysis, and healthy controls. In contrast, the second cytokine profile contained predominantly KTRs producing mainly Th[SUB]1[/SUB] cytokines upon re-stimulation, with lower levels or absence of Th[SUB]2[/SUB], Th[SUB]17[/SUB], and Th[SUB]9[/SUB] cytokines. Multivariate analyses indicated that a balanced memory T cell response with the production of Th[SUB]1[/SUB] and Th[SUB]2[/SUB] cytokines was associated with high levels of S1-specific binding and neutralizing antibodies mainly at 6 months after second vaccination. In conclusion, seroconversion is associated with the balanced production of cytokines by memory T cells. This emphasizes the importance of measuring multiple T cell cytokines to understand their influence on seroconversion and potentially gain more information about the protection induced by vaccine-induced memory T cells.
. 2023 May 17;8(1):70.
doi: 10.1038/s41541-023-00664-4. Th[SUB]1[/SUB]-dominant cytokine responses in kidney patients after COVID-19 vaccination are associated with poor humoral responses
Yvette den Hartog[SUP] 1 [/SUP], S Reshwan K Malahe[SUP] 1 [/SUP], Wim J R Rietdijk[SUP] 2 [/SUP], Marjolein Dieterich[SUP] 1 [/SUP], Lennert Gommers[SUP] 3 [/SUP], Daryl Geers[SUP] 3 [/SUP], Susanne Bogers[SUP] 3 [/SUP], Debbie van Baarle[SUP] 4 5 [/SUP], Dimitri A Diavatopoulos[SUP] 6 7 [/SUP], A Lianne Messchendorp[SUP] 8 [/SUP], Renate G van der Molen[SUP] 6 [/SUP], Ester B M Remmerswaal[SUP] 9 [/SUP], Frederike J Bemelman[SUP] 10 [/SUP], Ron T Gansevoort[SUP] 8 [/SUP], Luuk B Hilbrands[SUP] 11 [/SUP], Jan-Stephan Sanders[SUP] 8 [/SUP], Corine H GeurtsvanKessel[SUP] 3 [/SUP], Marcia M L Kho[SUP] 1 [/SUP], Marlies E J Reinders[SUP] 1 [/SUP], Rory D de Vries[SUP] #[/SUP][SUP] 3 [/SUP], Carla C Baan[SUP] #[/SUP][SUP] 12 [/SUP]; RECOVAC Consortium
Affiliations
- PMID: 37198189
- DOI: 10.1038/s41541-023-00664-4
Cytokines are regulators of the immune response against severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). However, the contribution of cytokine-secreting CD4[SUP]+[/SUP] and CD8[SUP]+[/SUP] memory T cells to the SARS-CoV-2-specific humoral immune response in immunocompromised kidney patients is unknown. Here, we profiled 12 cytokines after stimulation of whole blood obtained 28 days post second 100 μg mRNA-1273 vaccination with peptides covering the SARS-CoV-2 spike (S)-protein from patients with chronic kidney disease (CKD) stage 4/5, on dialysis, kidney transplant recipients (KTR), and healthy controls. Unsupervised hierarchical clustering analysis revealed two distinct vaccine-induced cytokine profiles. The first profile was characterized by high levels of T-helper (Th)[SUB]1[/SUB] (IL-2, TNF-α, and IFN-γ) and Th[SUB]2[/SUB] (IL-4, IL-5, IL-13) cytokines, and low levels of Th[SUB]17[/SUB] (IL-17A, IL-22) and Th[SUB]9[/SUB] (IL-9) cytokines. This cluster was dominated by patients with CKD, on dialysis, and healthy controls. In contrast, the second cytokine profile contained predominantly KTRs producing mainly Th[SUB]1[/SUB] cytokines upon re-stimulation, with lower levels or absence of Th[SUB]2[/SUB], Th[SUB]17[/SUB], and Th[SUB]9[/SUB] cytokines. Multivariate analyses indicated that a balanced memory T cell response with the production of Th[SUB]1[/SUB] and Th[SUB]2[/SUB] cytokines was associated with high levels of S1-specific binding and neutralizing antibodies mainly at 6 months after second vaccination. In conclusion, seroconversion is associated with the balanced production of cytokines by memory T cells. This emphasizes the importance of measuring multiple T cell cytokines to understand their influence on seroconversion and potentially gain more information about the protection induced by vaccine-induced memory T cells.